CSK
Tyrosine-protein kinase CSK
Also known as: CSK_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P41240
- Gene
- CSK
- Ensembl
- ENSG00000103653
- Chromosome
- 15
- Canonical length
- 450 aa
- Protein class
- Enzymes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Vesicles,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is involved in multiple pathways, including the regulation of Src family kinases. It plays an important role in T-cell activation through its association with the protein encoded by the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene. This protein also phosphorylates C-terminal tyrosine residues on multiple substrates, including the protein encoded by the SRC proto-oncogene, non-receptor tyrosine kinase gene. Phosphorylation suppresses the kinase activity of the Src family tyrosine kinases. An intronic polymorphism (rs34933034) in this gene has been found to affect B-cell activation and is associated with systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]
Canonical amino-acid sequenceUniProt
450 residues, UniProt reviewed canonical sequence.
>P41240|CSK
1 MSAIQAAWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA KNKVGREGII
61 PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE TGLFLVREST NYPGDYTLCV
121 SCDGKVEHYR IMYHASKLSI DEEVYFENLM QLVEHYTSDA DGLCTRLIKP KVMEGTVAAQ
181 DEFYRSGWAL NMKELKLLQT IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM
241 TQLRHSNLVQ LLGVIVEEKG GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE
301 AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV KWTAPEALRE
361 KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE KGYKMDAPDG CPPAVYEVMK
421 NCWHLDAAMR PSFLQLREQL EHIKTHELHLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CSK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.26
- Highest tissue expression
- 158 nTPM
Expression across tissuesHPA
Tissue
- lymph node: 158 nTPM
- spleen: 122 nTPM
- tonsil: 100 nTPM
- esophagus: 96 nTPM
- appendix: 84 nTPM
- thymus: 64 nTPM
Single-cell type
- esophageal apical cells: 201 nCPM
- neutrophils: 178 nCPM
- tuft cells: 150 nCPM
- monocytes: 123 nCPM
- megakaryocytes: 99 nCPM
- nk-cells: 89 nCPM
Immune cell
- eosinophil: 176 nTPM
- non-classical monocyte: 170 nTPM
- intermediate monocyte: 147 nTPM
- neutrophil: 131 nTPM
- naive B-cell: 114 nTPM
- T-reg: 107 nTPM
Brain region
- pons: 52 nTPM
- midbrain: 49 nTPM
- medulla oblongata: 48 nTPM
- spinal cord: 48 nTPM
- white matter: 45 nTPM
- thalamus: 45 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.17
- gnomAD pLI
- 1
- gnomAD missense Z
- 3.98
- DepMap mean gene effect
- -0.1
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adaptive immune response
- adherens junction organization
- cellular response to peptide hormone stimulus
- intracellular signal transduction
- negative regulation of bone resorption
- negative regulation of cell population proliferation
- negative regulation of ERK1 and ERK2 cascade
- negative regulation of Golgi to plasma membrane protein transport
- negative regulation of interleukin-6 production
- negative regulation of low-density lipoprotein particle clearance
- negative regulation of phagocytosis
- negative regulation of T cell activation
- negative regulation of T cell receptor signaling pathway
- oligodendrocyte differentiation
- protein phosphorylation
- regulation of Fc receptor mediated stimulatory signaling pathway
- T cell costimulation
- T cell receptor signaling pathway
Molecular functions
- ATP binding
- identical protein binding
- metal ion binding
- non-membrane spanning protein tyrosine kinase activity
- proline-rich region binding
- protein kinase A catalytic subunit binding
- protein phosphatase binding
- protein tyrosine kinase activity
- protein tyrosine kinase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- SH2 domain
- Serine-threonine/tyrosine-protein kinase, catalytic domain
- SH3 domain
- Tyrosine-protein kinase, active site
- Protein kinase-like domain superfamily
- Protein kinase, ATP binding site
- Tyrosine-protein kinase, catalytic domain
- CSK-like, SH2 domain
- SH3-like domain superfamily
- SH2 domain superfamily
- Non-receptor tyrosine kinases involved in cell signaling
- SH2 domain
- SH3 domain
- Protein tyrosine and serine/threonine kinase
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CSK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CSK as an antibody target. Whether an autoantibody or antibody against CSK could matter depends on whether native CSK is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CSK is annotated at the cell surface, where native CSK is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CSK as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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